GSK356278 is an effective and selective inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory, anxiolytic, and cognition-enhancing effects.

PDE4B:8.8 (pIC50), PDE4D:8.7 (pIC50), PDE4A:8.6 (pIC50)

GSK356278 bounds to the HARBS in rats, mice, marmosets, and ferrets with pKis of 7.9, 7.8, 8.4, and 8.5, respectively. GSK356278 inhibits LPS-induced release of TNF-α in human whole blood, with a pIC50 of 7.6. GSK356278 competes with [3H]rolipram for the high affinity rolipram binding site (HARBS) with a pKi of 8.6 in a competitive filtration-binding assay to the recombinant human PDE4B2B enzyme expressed in yeast membranes[1].

GSK356278 (4 doses at 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; p.o.) enhances performance in a nonhuman primate object retrieval test[1]. GSK356278 exhibits oral bioavailability (rat 91%, monkey 23%) and Cmax (rat 205, monkey 41 nM) following oral administration (rat 1, monkey 0.2 mg/kg). GSK356278 (0.1-0.1 mg/kg; p.o.) demonstrates efficacy in a nonhuman primate model of anxiety at exposures that do not induce emesis. GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding[1].